An approach to making risky research with pathogens safer

Editor’s note: This article is part of a collection of expert commentaries. You can read the rest of the series here. 

I once met with a minister of health about a problem involving a vaccine manufacturer and the national regulatory agency. Records from both the manufacturer and the regulator falsely and intentionally reported positive quality control results for a vaccine that did not appear to be protecting children from disease. As we discussed the problem, the minister threw up her hands in resignation. Regulations that are not enforced do little but provide a false sense of security, she said, tying this to the corruption she had witnessed.

The same regulatory problem applies to gain of function research that can enhance the dangerous characteristics of pathogens.

If scientists with research skills work in countries where, as in the case of vaccine production above, regulations cannot be fully enforced, the rules provide little actual security. Regulators may or may not be able to provide the appropriate level of oversight. Regulation is useful when based on known or presumptive evidence. But gain of function pathogen research is an emerging area, and the level of risk a given experiment entails or the value of any result it produces may not be fully understood. So regulation alone cannot fully mitigate the risks of this work, or the risks from insecure laboratories.

Gain of function research can create pathogens that don’t exist in nature, and it can potentially answer many questions about pathogen transmissibility and virulence. The enhancement of pathogens can lead to a greater understanding of genetic characteristics that contribute to those attributes, and there are examples of gain of function research—especially involving pathogens that cause respiratory disease such as influenza—that have added to scientific understanding of these pathogens.

Gain of function research can arouse concern because if the manipulated pathogen leaks from laboratory containment, it could cause a public health threat. A pathogen that could not previously spread easily from person to person might have gained the ability to do so.  It is therefore mandatory that gain of function research be conducted in bio-secure laboratories. But there are examples of leaks of dangerous but naturally occurring viruses, even from laboratories that were thought to be bio-secure, including leaks involving variola, the polio virus, and SARS-CoV-1.  Most of these leaks have occurred in highly industrialized and regulated economies.

Policy makers and political leaders often seek to decrease risks by imposing regulation from the top down, and they then consider that the risks are mitigated, be they from research itself or laboratories in which the research is conducted. Oversight cannot stop at regulations however—it also takes awareness and practice of well-established norms in research and biosecurity among the scientists who conduct gain of function research to ensure that they and the laboratories in which they work adhere to these norms.  And equally as important is the need to prevent non-essential and rogue research—research done by clandestine scientists applying dual use knowledge for purposes such as bioterrorism.

Certainly, decreasing the threat of risky research is easier said than done. To decrease the threat, governments and scientists might need to build policies and regulation from the bottom up, rather than imposing them from the top down. Reaching consensus among legitimate researchers and laboratory managers on risk mitigation measures, and providing the evidence supporting those measures to those who make policy and regulation, may be a good place to start. Peer-to-peer external review of safety procedures by and of researchers and laboratory managers would perhaps continue the process, as might a code of ethics for publishing procedures, genetic sequences, and other information that could empower rogue scientists—even though those measures might mean fewer publications and less publicly available information.

To ensure that necessary gain-of-function research is conducted in laboratories with maximum biosecurity, to define and prevent non-essential research, and to prevent rogue research that could endanger laboratory workers and the wider population constitutes a real challenge that will be best met by cooperation among governmental regulators and legitimate researchers and lab managers.